β淀粉样肽表达引起轴索线粒体数量减少但体积增大，提示线粒体的分裂障碍

1月27日，美国《神经科学杂志》（Journal of Neuroscience）发表了神经科学研究所黄福德研究小组及其合作者的{zx1}研究成果――“expression_r_r of β-Amyloid Induced Age-Dependent Presynaptic and Axonal Changes in Drosophila”。该项工作由神经所黄福德小组的赵晓亮，谭江秀，张潇，张保柱，王宇航，杨程韩宇以及上海交通大学的王文安，黄健康，朱红莲，孙晓江共同完成。

阿尔兹海默病（Alzheimer’s Disease,AD）是老年人中最常见的痴呆病。突触功能异常和突触丢失被广泛认为是AD痴呆症的细胞机制，但在AD中突触结构和功能异常的性质和进程基本未知。通过在特定组织中表达β淀粉样肽，作者在成虫果蝇中建立了一个AD模型。利用该模型对单个神经元的轴索和突触前的结构和功能进行了大量的时程检测，发现β淀粉样肽表达早期引起突触前线粒体减少，可能抑制了线粒体的分裂，随后引起一系列其它轴索和突触前结构与功能的变化。

该项工作得到了中国科学院、科技部以及上海市政府的项目资助。（Bioon.com）

生物谷推荐原始出处：

The Journal of Neuroscience, January 27, 2010, 30(4):1512-1522; doi:10.1523/JNEUROSCI.3699-09.2010

expression_r_r of β-Amyloid Induced Age-Dependent Presynaptic and Axonal Changes in Drosophila

Xiao-Liang Zhao,1 * Wen-An Wang,2 * Jiang-Xiu Tan,1 Jian-Kang Huang,3 Xiao Zhang,1 Bao-Zhu Zhang,1 Yu-Hang Wang,1 Han-Yu YangCheng,1 Hong-Lian Zhu,3 Xiao-Jiang Sun,3 and Fu-De Huang1

1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 2Department of Neurology, Xin Hua Hospital affiliated with Shanghai Jiaotong University School of Medicine, Shanghai 200233, China, and 3Department of Neurology, The Sixth People's Hospital affiliated with Shanghai Jiaotong University, Shanghai 200092, China

Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of β amyloid1-42 (Aβ) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Aβ accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Aβ. The depletion of presynaptic mitochondria was the earliest detected and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Aβ-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Aβ accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.